1. Field of the Invention
Chemical analysis of liquids such as water, foodstuffs like milk, and biological liquids is often desirable or necessary. Various elements to facilitate liquid analyses are known. Such elements have often included a reagent for a substance under analysis, termed analyte herein, which reagent, upon contacting a liquid sample containing the analyte, effects formation of a colored material or another detectable change in response to the presence of the analyte. Such elements include, for example, pH test strips and similar indicators wherein a paper or other highly absorbent carrier is impregnated with a material, chemically reactive or otherwise, that responds to contact with liquid containing hydrogen ion or other analyte and either generates color or changes color. Depending on the selection of responsive material, the change is usually qualitative or, at best, semiquantitative. In certain fields, it is often required that analytical techniques yield rapid, quantitative results. Much recent development work has attempted to provide elements useful in diagnostic chemical analysis, where testing of biological liquids including body fluids such as blood, plasma, urine and the like, must produce highly quantitative results, rapidly and conveniently.
Solution chemical techniques have enjoyed broad acceptance in the clinical laboratory environment, particularly in automated analysis. Such techniques, however, require analyzer equipment having intricate solution handling and transport capabilities. Analytical equipment of the "wet chemistry" variety, illustrated for example in U.S. Pat. No. 2,797,149, U.S. Pat. No. 3,036,893 and U.S. Pat. No. 3,526,480 is often expensive and cumbersome, and further requires skilled personnel, both for operation and the precise cleaning needed to avoid sample to sample contamination.
As an alternative to solution chemistry, various integral elements for non-solution chemical analysis have been proposed. Although essentially dry analysis offers substantial storage, handling and other conveniences as compared to wet chemistry, variations of the "dry" approach have enjoyed only limited success and have been used primarily for qualitative and semi-quantitative test purposes.
2. Description of Related Art
A basic variety of integral and analytical element is described in U.S. Pat. No. 3,092,465. Such multi-layer elements use an absorbent carrier impregnated with one or more reagents, typically including a color former, over which is coated a semipermeable membrane. Upon contact with a test liquid, analyte passes through the membrane which prevents passage and absorption of certain interfering components that could impair the test results. Such elements do not yield highly quantitative results. For such reasons they have not been popular in certain test situations, as in clinical laboratory applications.
Integral analytical elements adapted for automated test procedures have also been described, such as in U.S. Pat. Nos. 3,368,872 and 3,526,480. Such descriptions refer to means for avoiding chromatographic effects (often called ringing, targeting or doughnuting) in the element by immobilizing reagent or including a means to decrease the tendency of an applied sample to exert a washing effect on incorporated reagent, as by use of simple porous members over a reagent carrying material. However, there is no suggestion of an efficient means to provide a uniform concentration of analyte to all reagent areas contacted by an applied sample, and such balanced concentration is extremely important if test results are to be interpretable by automated readout, whether densitometric, colorimetric, fluorometric, or otherwise.
The only disclosed means to provide a somewhat uniform concentration of analyte to an element's reagent areas has been by a technique that can be termed sample confinement. Usually, as is described in U.S. Pat. No. 3,368,872, a barrier is included on the element to confine an applied sample in a predetermined region of the element's surface, with the result that excess liquid is usually present on the element after sample application. This can create inconvenience in handling and cleanup and, more seriously, can require precise sample volume delivery when applying sample to the element.
There has been some recognition of the need to promote or avoid, as desired, the migration of reagents and sample constituents between layers of integral analytical elements, as is discussed in U.S. Pat. Nos. 2,761,813; 2,672,431; 2,672,432; 2,677,647; 2,923,669; 3,814,670 and 3,843,452. However, this has been in the context of elements for microbiological analysis. Such elements either do not indicate any means to effect or preserve concentrational uniformity, for example laterally within a layer, as by isotropic porosity or uniform permeability, or they require blended layers the interface of which is characterized by mutual penetration of the adjacent layers.
There is no suggestion in the related art that sample constituents should be encouraged to distribute within one layer to achieve therein concentrational unifomity for analyte or other substances that can be provided, still in uniform concentration, to an associated layer for analytical reactions or similar activity. In fact, the structural and chemical characteristics of materials used in the microbiological element (such as absorbent papers, wood, etc.) might impair such a result for reasons of physical restraint, non-uniform permeability or undesirable chemical binding. Additionally, the choice of fibrous absorbent materials could further frustrate highly accurate measurement, due to their nonuniform structure and texture.
As can be appreciated, obstacles to the more widespread use of elements for essentially dry analysis have included the inability of previous elements to produce highly quantitative, uniform test results and their lack of compatibility with machine handling and the automated readout and processing of test results. Improved elements are needed, particularly those able to perform the various sample handling and reaction functions apparently necessary to overcome problems such as those mentioned previously herein.